# Correction of Immune Response Improves Aged Fracture Healing

> **NIH NIH R21** · DUKE UNIVERSITY · 2021 · $161,000

## Abstract

ABSTRACT
 Bone fractures occur in 50% of the population causing significant morbidity and mortality and costing
more than $20 billion in health care annually. Fracture repair is a complex process that involves numerous
signaling molecules and cellular processes, all of which have not been fully identified. Factors, such as advanced
age, can negatively affect this process thereby impairing recovery and proper bone healing. Our preliminary data
indicate that macrophages recruited to the site of bone injury in young mice create a niche that leads to robust
tissue repair. With age, the constituents of the secreted niche are lost resulting in diminished bone healing. Our
previous parabiosis and bone marrow transplant models as well as in vitro cell culture studies have confirmed
that the young macrophage niche is able to improve fracture repair and osteoblast differentiation in aged mice.
Notable within these investigations, rejuvenation coincided with decreased numbers of classically activated, pro-
inflammatory, M1 macrophages at the site of injury but increased alternatively activated, regenerative, M2
macrophages. To recapitulate these findings using a therapeutic approach, we treated a small cohort of aged
mice with Maresin1 shortly after bone fracture injury. Relative to vehicle controls, treated mice displayed
decreased, control inflammation after injury and the fracture calluses from these mice contained more mineral.
Furthermore, media conditioned by macrophages treated with Maresin1 improved aged osteoblast
differentiation, matrix production, and mineral formation. Within the proposed work here we will identify the
mechanism by which Maresin1 treatment improves bone fracture healing and determine the constituents of the
niche secreted by macrophages which improves aged osteoblast function.

## Key facts

- **NIH application ID:** 10266845
- **Project number:** 5R21AG067245-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Gurpreet Baht
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $161,000
- **Award type:** 5
- **Project period:** 2020-09-30 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10266845

## Citation

> US National Institutes of Health, RePORTER application 10266845, Correction of Immune Response Improves Aged Fracture Healing (5R21AG067245-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10266845. Licensed CC0.

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